This disclosure pertains to a method for assessing changes in biomechanical properties of ocular and other tissues and for detecting and differentiating tissue stiffness using optical coherence elastography (OCE).
The changes in viscoelastic properties of the tissues are associated with onset and progression of different diseases. Therefore, it is important to assess and quantify tissue mechanical properties during disease progression and application of different therapeutic procedures.
For example, keratoconus is associated with localized reduced rigidity of the cornea, and the information of the corneal stiffness is useful to provide improved diagnosis and monitoring of this pathological status. Also, real-time in vivo measurement of the spatial elasticity distribution with microscopic scale in the cornea could lead to adaptive mechanical modeling of the individual corneal structure which is extremely important to prevent over-corrections, under-corrections and ectasia from refractive surgeries, such as LASIK, and to further optimize the laser ablation procedures.
Structurally degenerative diseases such as keratoconus can significantly alter the stiffness of the cornea, directly affecting the quality of vision. Keratoconus can pathologically decrease the stiffness of the cornea, leading to a loss in the quality of vision. Detecting changes in the biomechanical properties of ocular tissues, such as stiffness of the cornea, can aid in the diagnosis of these structurally degenerative diseases.
As another example, changes in mechanical properties of crystalline lens play an important role in the development of presbyopia, which is the progressive, age-related loss of accommodation of the eye. Results of ex-vivo studies have shown that the stiffness of crystalline lenses increases with age for animals and humans. The increase in lens stiffness is generally believed to be responsible for the progressive loss of the ability of the lens to change shape, leading to presbyopia. However, current understanding of the mechanical properties of the lens, its changes with age, and its role in presbyopia is limited, in part due to a lack of technology that allows measurements of the mechanical properties of the lens in situ and in vivo. The location of the crystalline lens inside the eye makes it challenging to measure its mechanical properties in vivo or in situ (i.e., inside the globe).
UV-induced collagen cross-linking (CXL) is an emerging treatment that effectively increases corneal stiffness and is applied clinically to treat keratoconus. The effectiveness of this treatment may be analyzed by measuring the corneal stiffness both before and after treatment. However, measured corneal stiffness is also influenced by intraocular pressure (IOP). Therefore, experimentally measured changes in corneal stiffness may be attributable to the effects of CXL, changes in IOP, or both. There is a possibility that a cornea, particularly after treatment with CXL, may still be structurally weakened by keratoconus, yet have a “normal” measured stiffness due to an elevated IOP. Current techniques are not able to measure the true IOP in vivo without consideration of the effect of the biomechanical properties of the cornea. Distinguishing corneas that have the same measured stiffness but are at different IOPs is still a challenge.
Elastography is an emerging technique that can map the local mechanical properties of tissues. Ultrasound elastography (USE) and magnetic resonance elastography (MRE) have experienced rapid development during the past few years as diagnostic tools. One common principle of these techniques is correlating tissue deformation caused by the external mechanical excitation to tissue elasticity. In previous studies, acoustic radiation force was applied to a microbubble created by laser-induced optical breakdown in the lens. The displacement of the microbubble was measured by ultrasound and used to evaluate lens elasticity. However, such approach is required to produce microbubbles within the lens. The basic feasibility of using Brillouin microscopy to measure the lens bulk modulus both in vitro and in vivo has been explored. Brillouin microscopy can be implemented using simple instrumentation, but it has a relatively slow acquisition time. There is also uncertainty on how to correlate Brillouin shift (modulus) to the classical mechanical description of the tissues (e.g. Young modulus). USE and MRE can assess mechanical properties of tissue but the relatively low spatial resolution of USE and MRE is still a critical limitation for certain applications, particularly for ocular tissues and also for measurements at the cellular level.
What is needed, therefore, is an improved, non-invasive and highly sensitive method to assess the mechanical properties of the ocular and other tissues with high resolution and sensitivity.